反応 #168228

反応方程式

2,3-dichloro-5-(3-methoxyphenyl)isonicotinonitrile

o-toluidine

→

3-chloro-5-(3-methoxyphenyl)-2-(o-tolylamino)isonicotinonitrile

溶媒

ethyl acetate

DMSO

反応条件

後処理

1. 1
   温度The mixture was cooled to room temperature
2. 2
   洗浄washed with 1 N HCl (5 mL), water (5 mL), brine (5 mL)
3. 3
   乾燥dried (MgSO4)
4. 4
   濃縮concentrated
5. 5
   その他Purification by reverse phase HPLC (Sunfire S10 30×250 mm column)
6. 6
   洗浄eluting with 80-100% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA)

実験手順

A mixture of 2,3-dichloro-5-(3-methoxyphenyl)isonicotinonitrile (50 mg, 0.179 mmol, from Step 3 of Example 128) and o-toluidine (384 mg, 3.58 mmol) in DMSO (1 mL) was heated to 180° C. under microwave for 1 h. LCMS and HPLC analysis indicated that the reaction was ˜25% complete. The mixture was cooled to room temperature, diluted with ethyl acetate (60 mL), washed with 1 N HCl (5 mL), water (5 mL), brine (5 mL), dried (MgSO4) and concentrated. Purification by reverse phase HPLC (Sunfire S10 30×250 mm column), eluting with 80-100% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA), gave 3-chloro-5-(3-methoxyphenyl)-2-(o-tolylamino)isonicotinonitrile as yellow solid, assumed as TFA salt (7 mg, 8% yield). 1H NMR (400 MHz, methanol-d4) δ ppm 8.13 (1H, s), 7.38-7.54 (2H, m), 7.28-735 (1H, m), 7.15-7.27 (2H, m), 7.07-7.14 (2H, m), 6.97-7.05 (1H, m), 3.87 (3H, s), 2.27 (3H, s); MS (ES+) m/z: 350 (M+H); LC retention time: 3.848 min (analytical HPLC Method A).

出典